Our description and investigations of combined immunodeficiency (CID) in young horses has demonstrated that this fatal genetic defect in foals is very similar to CID in children. Our objectives are 1) to further define the defect in foals by characterizing the in vivo and in vitro B and T-lymphocite responses to antigens and plant lectins. Closely related foals to those with CID will be evaluated for lymphocyte defects. Also, the complement systems, secretory component and function of the epithelial cells of the hypoplastic thymuses will be evaluated. Another objective 2) is to determine the biochemical defect and/or its expression in the lymphoid system and relate these findings to the absence of antibody and cell mediated immunity. The amounts of adenosine deaminase in CID and normal foals will be determined since some CID children are deficient in this enzyme. Also, the mixed lymphocyte culture response of CID and carrier horses will be studied to determine if abnormalities are present. Attempts to induce CID stem cells to produce committed lymphocytes will be made. The last objective 3) is to attempt methods of therapy in CID foals which may be useful for treatment of children with similar defects. We will try to reconstitute B- and T-cell function with fetal liver transplants and T-cell function with fetal thymus transplants. These treatments may avoid graft versus host reactions if young fetuses are used. Transfer factor will be evaluated for its role in CID foals. Finally, correction of the defect in foals will be attempted with metaphase chromosomes from normal bone marrow stem cells.